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Hum Gene Ther. 2018 Apr;29(4):492-506. doi: 10.1089/hum.2017.120. Epub 2018 Jan 22.

Delivery of Adeno-Associated Virus Vectors in Adult Mammalian Inner-Ear Cell Subtypes Without Auditory Dysfunction.

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1 Department of Otolaryngology and Program in Neuroscience, Harvard Medical School and Eaton Peabody Laboratory, Massachusetts Eye and Ear Infirmary , Boston, Massachusetts.
2 Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China .
3 Department of Otolaryngology-Head and Neck Surgery, Eye and ENT Hospital, Shanghai Medical College, Fudan University , Shanghai, China .
4 Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Medical School of Chinese PLA , Beijing, China .
5 Department of Ear, Nose and Throat, People's Hospital of Jilin Province , Changchun, China .
6 Grousbeck Gene Therapy Center, Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary , Boston, Massachusetts.
7 Ocular Genomics Institute, Department of Ophthalmology, Harvard Medical School , Boston, Massachusetts.
8 Horae Gene Therapy Center and Department of Microbiology and Physiological Systems, University of Massachusetts Medical School , Worcester, Massachusetts.
9 State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu, China .


Hearing loss, including genetic hearing loss, is one of the most common forms of sensory deficits in humans with limited options of treatment. Adeno-associated virus (AAV)-mediated gene transfer has been shown to recover auditory functions effectively in mouse models of genetic deafness when delivered at neonatal stages. However, the mouse cochlea is still developing at those time points, whereas in humans, the newborn inner ears are already fully mature. For effective gene therapy to treat genetic deafness, it is necessary to determine whether AAV-mediated therapy can be equally effective in the fully mature mouse inner ear without causing damage to the inner ear. This study tested several AAV serotypes by canalostomy in adult mice. It is shown that most AAVs transduce the sensory inner hair cells efficiently, but are less efficient at transducing outer hair cells. A subset of AAVs also transduces non-sensory cochlear cell types. Neither the surgical procedure of canalostomy nor the AAV serotypes damage hair cells or impair normal hearing. The studies indicate that canalostomy can be a viable route for safe and efficient gene delivery, and they expand the repertoire of AAVs to target diverse cell types in the adult inner ear.


AAV; adult mouse; hair cells; hearing; inner ear

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